tbuckley/cabot-search huggingface dataset:
Is it safe and effective to increase the energy dose accumulated in the lithiasis by increasing the number of shock waves per session in extracorporeal lithotripsy? New prospective and randomized study
Authors: J.D. López Acón, A. Budía Alba, J. Bolón Marset, B. Nakdali Kassab, D.G. Ordaz Jurado, M. Trassierra Villa, P. Bahilo Mateu, F. Boronat Tormo
Journal: European Urology (2022)
How has the COVID-19 pandemic influenced prostate cancer? Tertiary uni-center analysis of diagnosis and treatment times
Authors: C. Minguez Ojeda, S. Garcia Barreras, J.A. López Plaza, S. Arribas Terradilla, A. Dominguez Guitierrez, G. Fernandez Conejo, E. Sanz Mayayo, A. Fraile Poblador, R. Rodriguez Patrón, F.J. Burgos Revilla
Journal: European Urology (2022)
Elevated hemoglobin: Creatinine ratio is a novel preoperative marker for worsened survival outcomes in upper tract urothelial carcinoma: Analysis from the robuust registry
Authors: M.F. Meagher, R. Autorino, R. Mehrazin, D. Eun, V. Margulis, R. Uzzo, J. Porter, C. Sundaram, F. Abdollah, A. Mottrie, A. Minervini, M. Ferro, H. Dialadat, Z. Wu, K. Hakimi, A. Saidian, A. Walia, R. Tellini, A. Veccia, E. Mazzone, R. Koon, M. Gonzalgo, I. Derweesh
Journal: European Urology (2022)
Assessing association of heavy metal levels in urine and sera with neurotoxicity in breast cancer(BC) patients undergoing adjuvant/neoadjuvant chemotherapy.
Authors: Kristen Danielle Whitaker, Eric A. Ross, James E. Klaunig, Tanu Singh, Rosanna Veggeberg, Katherine Alpaugh, Lori J. Goldstein
Journal: Journal of Clinical Oncology (2022)

e12510 Background: Standard adjuvant chemotherapy for early stage BC includes taxane therapy with paclitaxel or docetaxel. Taxanes are associated with peripheral neuropathy in some patients, which can impact appropriate dosing and quality of life. In this study, we investigated whether there is an association between the levels of heavy metals in serum or urine and the development of high-grade peripheral neuropathy, defined as grade ≥2 (utilizing CTCAE v.4.0) in a cohort of BC patients undergoing neo/adjuvant taxane chemotherapy. Methods: BC patients undergoing treatment with taxanes were identified in the clinic. Patient eligibility included: histologically confirmed invasive mammary carcinoma, Stage I-III BC, undergoing neo/adjuvant treatment with taxane chemotherapy. Patients previously treated with chemotherapy or who had pre-existing neuropathy were not eligible. Patients were consented and prior to study enrollment, study participants provided blood and urine samples to assess for heavy metals. Neurotoxicity was measured using the NCI CTCAE v.4 criteria throughout patient’s taxane treatment. Serum and urine samples collected at baseline were analyzed for heavy metals by inductively coupled plasma mass spectrometry (ICP-MS). Results: 115 female patients were enrolled. 111 patients were included in the analysis; 4 patients were excluded due to withdrawal from study prior to receiving any taxane treatment. Participants were 78% White (6% of Hispanic origin), 19% Black and 3% Asian with an average age of 51 years (range 26-72). ICP-MS was used for the analysis of Aluminum (Al), Manganese (Mn), Cobalt (Cu), Zinc (Zn), Arsenic (As), Cadmium (Cd), Mercury (Hg), Thallium (Tl), and Lead (Pb) levels in patients’ serum and urine. Patients with neurotoxicity grade &gt;=2 had significantly lower serum Arsenic levels (mean=0.37 [SD=1.08], n=89] than subjects with toxicity grades 0-1 [mean=1.21 (SD=2.33), n=22] (p=0.037; Wilcoxon test). Other than Arsenic no relationship of the other heavy metals and neurotoxicity was found in the serum. We did not observe significant associations between heavy metal levels in urine and neurotoxicity grade. Conclusions: Taxane treatment is an effective BC therapy but its utility is limited by its associated toxicity of peripheral neuropathy. The source of the higher arsenic levels is unclear. We conclude that there is no evidence that high levels of heavy metals were associated with taxane induced neurotoxicity in our study.
SURG-03. Durability of an Early Management Strategy Facilitating Endoscopic Removal of Recurrent Choroid Plexus Carcinoma
Authors: Sergio Guadix, Tyler Garman, David Pisapia, Mark Souweidane
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Choroid plexus carcinoma (CPC) is a rare, primarily intraventricular neoplasm with a dismal prognosis. Extent of surgical removal is correlated with improved outcomes but is frequently limited due to tumor vascularity and size. Information related to surgical management and molecular drivers of tumor recurrence is currently limited. Here we characterize a case of multiply recurrent CPC treated solely with sequential endoscopic tumor removals over a 10-year period and highlight its genomic properties. METHODS: We performed a retrospective review of a 16-year-old female treated for CPC with local and distal recurrences undergoing repeat excision with minimally invasive neuro-endoscopy. We describe technical nuances associated with neuro-endoscopic intervention, mean hospital stay, complications, and perioperative MRI. Whole exome sequencing (WES), targeted sequencing, and methylation profiling results over time are reviewed. RESULTS: Five years after standard treatment, the patient was evaluated for a distant intraventricular recurrence. A total endoscopic resection was performed given the local, non-disseminated recurrence pattern. WES results included NF1, PER1, and GLI3 mutations as well as FGFR3 gain, and was negative for TP53 alterations. Repeat sequencing on a recurrence 4 years later showed persistent NF1 and FGFR3 alterations. Methylation profiling was consistent with “plexus tumor, subclass pediatric B”. Overall, short-term surveillance neuroimaging detected four isolated recurrences, all treated with complete endoscopic resections at 5 years, 6.5 years, 9 years, and 10 years after initial CPC diagnosis. Mean hospital stay for all recurrences was 1 day with no complications from treatment. CONCLUSION: We describe a patient with 4 isolated recurrences of CPC over a decade, each treated with complete endoscopic removal, and identify an unusual set of molecular alterations that persisted over time. These outcomes support a strategy encompassing frequent neuroimaging surveillance to facilitate a minimally invasive endoscopic surgical approach at early detection and relatively low tumor mutagenicity.
ETMR-08. Treatment strategy for pineoblastoma in infant
Authors: Mario Suzuki, Yuzaburo Shimizu, Osamu Akiyama, Junya Fujimura, Akihide Kondo
Journal: Neuro-Oncology (2022)

Abstract Pineoblastoma is a rare malignant brain tumor that occurs in infancy and young adulthood. Although its prognosis has improved in recent years, it remains one of the difficult tumor types to treat. We will retrospectively review the treatment of pineoblastoma at our hospital and propose the possibility of a new treatment for this tumor type. Three cases were studied. All of them presented at less than three years of age and were treated for hydrocephalus simultaneously as the biopsy. Chemotherapy was administered after a possible resection, and local radiotherapy was administered at the age of 3 years. Overall survival ranged from 7 to 91 months, with one case of long-term survival. To date, the prognostic factors for pineoblastoma are the age of onset and the presence of radiation therapy. This is interpreted to mean that the prognosis is worse in infants and young children who cannot be immediately treated with radiation therapy, indicating that radiation therapy is essential for treating this tumor type. On the other hand, radiation therapy for infants can significantly interfere with the development of the central nervous system, and there is much controversy about its potential compatibility with tumor control. We have identified a favorable prognosis group based on the molecular biological background of this tumor type. We propose that early radiotherapy may improve the prognosis.
Use of next-generation sequencing (NGS) to study the impact of demographic variables on prevalence of driver mutations in non-small cell lung cancer (NSCLC).
Authors: WonSeok William Choi, Faysal Haroun
Journal: Journal of Clinical Oncology (2022)

e21030 Background: The management of NSCLC is rapidly evolving with the discovery of new driver mutations and the introduction of targeted therapies (TT). The list of targets with FDA-approved TT is estimated to cover over half of the cases of non-squamous NSCLC. The prevalence of driver mutations varies significantly depending on several demographic variables such as smoking status, race, and sex. This abstract presents data obtained from a unique, racially diverse cohort of patients in the Washington, DC metropolitan area. Methods: Retrospective review of circulating tumor DNA NGS data from 2 commercial testing companies (Guardant and Tempus) and demographic data from our health records on 66 patients with NSCLC treated at the George Washington University Medical Faculty Associates between October 2017 and November 2021 was performed. Demographic information including age, sex, race, and smoking history, as well as histology, stage at diagnosis, and driver mutations were collected. Only patients with non-squamous NSCLC and identifiable mutations were included. Results: Mean age was 67. Most patients in this cohort were female (56.1%, male 43.9%), African-American (62.1%, Caucasian 25.8%, African 9.1%, Asian 3.0%), had smoking history (former smoker 48.5%, current smoker 25.8%, never smoker 25.8%), had adenocarcinoma (78.8%, other NSCLC (not squamous cell carcinoma or adenocarcinoma) 21.2%) with advanced stage (stage 4 62.1%, stage 3 28.8%, stage 1 3.0%, unknown 6.1%). Mutations are listed as follows: KRAS 28.8% (G12C accounted for 58% of all KRAS mutations), EGFR 19.7% (exons 19 and 21 mutations such as del19 and L858R accounted for 69%), MET 9.1% (MET amplification made up 83%), Her2 3.0% (2/66), ALK 3.0% (2/66), RET 1.5% (1/66), non-targetable mutations 34.8% (23/66). A table at the end of this abstract shows the frequency of three most prevalent mutations in this cohort distinguished by race, sex, and smoking status. Conclusions: KRAS was the most prevalent driver mutation in this cohort, followed by EGFR and MET. In concordance with the existing literature, EGFR was more prevalent in non-smokers and females, while KRAS was more common among smokers. Interestingly, a larger percentage of Africans had EGFR mutations compared to African-Americans. Given the small sample size, however, a larger scale study is needed to investigate this further. These findings show that demographic factors influence the prevalence of driver mutations which can have therapeutic implications in patients with NSCLC.[Table: see text]
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Kaposi sarcoma (KS) arises after Kaposi sarcoma herpesvirus infection and frequently develops in HIV-positive individuals. Ramaswami and colleagues conducted a clinical trial of pomalidomide, an oral immunomodulating thalidomide derivative, in patients with KS with or without HIV. The overall response rate was 71%, with 67% of HIV-positive patients and 80% of HIV-negative participants showing a response. Baseline IL-6 levels were higher in nonresponders compared with responders, although further assessment of IL-6 as a biomarker is warranted. Based on these results, the United Stated Food and Drug Administration granted accelerated approval to pomalidomide for the treatment KS.TIGIT is a novel target in the field of cancer immunotherapy. To explore the potential of anti-TIGIT immunotherapy, Mettu and colleagues conducted a phase 1a/b study to evaluate the safety, tolerability, and preliminary efficacy of the novel anti-TIGIT antibody etigilimab alone (phase 1a) and in combination with the anti-PD-1 nivolumab (phase 1b) in patients with refractory solid tumors. This first-in-human study showed etigilimab was well tolerated. Signs of anti-tumor activity were observed, with eight patients showing stable disease and one patient showing a partial response. Biomarker analyses demonstrated evidence of clear dose-dependent target engagement by etigilimab. These findings lay a foundation for future clinical trials targeting TIGIT.Detecting neuroendocrine prostate cancer (NEPC) in men with metastatic castration-resistant prostate cancer (mCRPC) has important prognostic and therapeutic implications but is challenging in clinical practice. To address this unmet need, Berchuck and colleagues developed a noninvasive biomarker, termed NEPC Risk Score, based on tissue-informed cell-free DNA (cfDNA) methylation analysis. Applying the NEPC Risk Score to cfDNA from two independent mCRPC cohorts discriminated between men with versus without NEPC with high accuracy. These data support the further clinical development of this cfDNA methylation-based biomarker to noninvasively identify men with NEPC who should be considered for platinum-based chemotherapy or clinical trials of NEPC-directed therapies.PD-1 blockade has provided benefit for some patients with advanced sarcomas. However, predicting response is not feasible currently. Furthermore, the relevance of hyperprogressive disease (HPD) is unclear. Klemen and colleagues performed a pooled analysis of prospective trials evaluating checkpoint inhibition in patients with sarcoma. In total, 134 patients were assessed, of which 16% had a complete or partial response, 36% had stable disease, 34% had progressive disease without HPD, and 11% with HPD. Patients with HPD and non-HPD progressive disease showed similarities in terms of disease subtype, clinical features, and genomic alterations. Interestingly, patients developing HPD had smaller tumors at baseline than patients who progressed without HPD. Additional clinical studies will be required to further understand HPD in patients with sarcoma.
Tumor necrosis or cavity on baseline CT scan as a negative predictive biomarker for immune checkpoint inhibitors in advanced lung squamous cell carcinoma.
Authors: Feng Long, Gen Lin, Xinlong Zheng, Kan Jiang, Qian Miao
Journal: Journal of Clinical Oncology (2022)

e20556 Background: Current predictive biomarker for immune checkpoint inhibitors (ICIs) does not distinct according to histologic subtype. We hypothesize that necrosis or cavity on baseline CT scan in lung squamous cell carcinoma (LSCC) is predictive of treatment for ICIs. Methods: This was a multicenter retrospective analysis of patients with advanced LSCC. All eligible patients must had received either first-line chemotherapy only (chemotherapy group), or ICIs as monotherapy or combined with chemotherapy (ICIs group). Radiotherapy to thorax was not allowed. Baseline contrast-enhanced CT were reviewed by independent radiologist in each center. Radiologic finding was correlated with outcomes. Results: Total of 538 patients were eligible with 270 patients in the chemotherapy group and 268 patients in ICIs group. Baseline characteristics were well balanced. Tumor necrosis or cavity was identified in 111 (41.1%) in chemotherapy group and 99 (36.9%) in ICIs group. In chemotherapy group, there was no difference in PFS between patients with or without necrosis or cavity (5.33 vs 4.97 months, Hazard Ratio (HR) 1.05, 95% confidence interval (CI), 0.81-1.36, p= 0.726). In contrast, there was significant difference in PFS in ICIs group favoring patients without tumor necrosis or cavity (8.7 vs 6.5 months, HR 0.67, 95% CI 0.42–0.63, p&lt; 0.001). Multivariate Cox analysis confirmed necrosis or cavity as an independent unfavorable predictive factor for PFS (HR 0.68; 95% CI, 0.51-0.9; p= 0.007). Conclusions: Tumor necrosis or cavity on baseline chest CT scan is a promising predictive biomarker for ICIs in LSCC, and this observation warrant further investigation.
Penpulimab plus gemcitabine in combination with cisplatin or anlotinib as first-line treatment for metastatic nasopharyngeal carcinoma (M NPC): A phase II study.
Authors: Shuang Huang, Xiaozhong Chen, Song Qu, Shenhong Qu, Yaqian Han, Kunyu Yang, Shiting Huang, Min Li, Lin Zhang, Qian Ding
Journal: Journal of Clinical Oncology (2022)

e18032 Background: Cisplatin (P)-based combination regimen is the backbone in the first-line treatment of M NPC while the toxicity limited its usage. This study investigated the efficacy and safety of penpulimab (an anti-programmed death-1 antibody) plus gemcitabine (G) in combination with cisplatin (P) or anlotinib (a multikinase inhibitor) as first-line treatment of these pts. Methods: This is a multicenter, three cohorts, randomized, phase II study (NCT04736810). Pts with histologically confirmed regional or distant M NPC who had measurable lesions per RECIST 1.1 and received no systemic treatment for metastatic lesions were enrolled. Other inclusion criteria included 18-75 years old and ECOG PS 0-1. Pts in cohort A, B and C were given G + P + penpulimab + anlotinib; G + P + penpulimab or G + penpulimab + anlotinib, respectively. G (1000mg/m 2 , d1, d8) and P (80mg/m 2 , d1) were given intravenously for 4 to 6 cycles, 3 weeks per cycle. Penpulimab (200mg, d1) and anlotinib (12mg, qd, d1-14) were given intravenously and orally respectively until confirmed disease progression, or unacceptable toxicities, or up to 2 years, whichever occurred firstly. Pts who developed disease progression but still had clinical benefit could receive penpulimab and anlotinib continuously based on the decision of physicians. The primary endpoint was objective response rate (ORR). Here we report the preliminary results of this study. Results: Between March 2021 and September 2021, 17 pts were randomly assigned to cohort A (n = 5), B (n = 5) or C (n = 7), and the median age was 52, 49 and 52 years old, respectively. Nearly half (7/17, 41.2%) had liver metastasis and the majority (5/7, 71.4%) was in the cohort C. At the data cutoff date on January 17, 2022, the median treatment cycles were 6, 8, 8 across three cohorts. All pts received tumor response and the confirmed ORR was 80.0%, 80.0% and 100%. The details of tumor response were summered in followed table. Notably, in cohort C, 1 pts achieved confirmed complete response (CR) and all others had confirmed partial response (PR). Replacement of cisplatin with anlotinib seemed to show better safety profile that ≥ grade 3 adverse events (AEs) occurred in 6 pts (85.7%) in cohort A, 5 (100%) in cohort B while only 4 (57.1%) in group C. Moreover, the overall incidence of serious AEs was 28.6%, 20%, 14.3% across three cohorts. The most common ≥ grade 3 AEs were white blood cell decreased and neutrophil count decreased. Conclusions: This preliminary analysis indicated that penpulimab plus gemcitabine and anlotinib had promising efficacy and favorable tolerance profile as first-line treatment for M NPC. Further investigate is ongoing. Clinical trial information: NCT04736810. [Table: see text]
Multiplexed apolipoprotein profiling advances the assessment of residual lipid-related cardiovascular risk
Authors: L Schmidt, R Clarke, A Von Ende, X Yin, K Theofilatos, J Hopewell, M Mayr
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background and Purpose Low-density lipoprotein cholesterol (LDL-C) is among the conventional lipid parameters used to predict risk of cardiovascular disease (CVD). Statins lower blood levels of pro-atherogenic LDL-C, but a residual cardiovascular risk remains in some individuals with therapeutically optimised LDL-C levels. Although the metabolism of LDL-C and other lipoprotein particles is governed by a range of different apolipoproteins, only apolipoproteins A-I and B are measured in clinical assays. Using a more comprehensive apolipoprotein panel in a large epidemiological cohort, this study aimed to determine the association of individual apolipoprotein levels with risk of coronary heart disease (CHD). Methods Bottom-up multiple reaction monitoring–mass spectrometry (MRM–MS) was used in conjunction with stable isotope-labelled peptide standards to quantify plasma levels of 13 apolipoproteins in participants of the Precocious Coronary Artery Disease (PROCARDIS) study (N = 1916; 941 cases of CHD, 975 controls). The relationship between apolipoprotein levels and CHD was assessed after adjusting for established risk factors for CVD and correcting for statin use. Results The strongest positive associations with CHD in the PROCARDIS study were seen for triglyceride-related apolipoproteins C-I (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.63–3.46), C-III (OR 2.95, 95% CI 1.85–4.71) and E (OR 2.35, 95% CI 1.54–3.58), as well as for apolipoprotein (a) (kringle IV type 2 repeat, OR 2.84, 95% CI 2.04–3.95). Comparing these with associations of apolipoproteins with CVD in the Bruneck study (N = 688) revealed consistency across the two cohorts. Robust inverse associations with CHD were observed for apolipoproteins A-IV (OR 0.45, 95% CI 0.31–0.65) and M (OR 0.29, 95% CI 0.19–0.44). Conclusion Analysing two large epidemiological cohorts, Bruneck and PROCARDIS, demonstrated that multiplexed apolipoprotein profiling improves the understanding of cardiovascular risk independent of conventional lipid parameters. Most prominently, triglyceride-related apolipoproteins were shown to positively associate with residual cardiovascular risk. The findings of this study support the need for development and implementation of standardised, MRM–MS-based apolipoprotein profiling assays to guide novel lipid-modifying therapies beyond statins.
Neutropenia as a predictor of efficacy in the treatment of metastatic colorectal cancer with TAS-102 (trifluridine - tipiracil).
Authors: Maria Yeray Rodriguez Garcés, Loreto Domínguez Senín, María Amor Urbano, Victoria Aviñó Tarazona
Journal: Journal of Clinical Oncology (2022)

e15564 Background: TAS-102 (trifluridine - tipiracil) increases the survival of patients with metastatic colorectal cancer (mCRC) in 3rd or successive lines based on the results in overall survival (OS) of the phase 2 trial by Yoshino T et al and of the subsequent phase 3 RESOURCE and TERRA. It has a good toxicity profile, mainly at the gastrointestinal and hematological levels. Different publications relate neutropenia secondary to this drug with greater clinical benefit. Methods: Retrospective and multicenter observational study with patients diagnosed with mCRC treated with TAS-102 in the Juan Ramón Jiménez and General de Río Tinto hospitals (Huelva) between January 2016 and September 2021. We describe demographic data and other variables; subsequent Cox regression and multivariate analysis between OS and the different variables. We represent the OS median using Kaplan-Meier curves. Results: 47 patients were included. Median age 66 years; 66% men. No patient with ECOG &gt; 2. Primary colon tumor in 55.4%; 72.3% with various metastatic locations. KRAS mutation in 63.8%. 78.8% in third line and the rest in fourth or successive. 80.9% have died. 82.9% abandoned due to progression and 8.5% due to toxicity: anemia 76.6% (grade ≥3 4.3%), neutropenia 74.5% (grade ≥3 44.7%), thrombocytopenia 10, 6% (grade ≥3 2.1%) and gastrointestinal 44.7% (grade ≥3 6.4%). The Kapplan Meier shows significant differences between the neutropenia curves 0 and grade 3-4 (median: 8 (95% CI 5.91-10.08) vs. 19 (95% CI 16.55-21.44) months; p = 0.043) and between the curves for grade 1-2 and grade 3-4 neutropenia (median: 8 (95% CI 2.9-13.09) vs. 19 (95% CI 16.55-21.44) months; p = 0.019). Cox regression identified grade 3-4 neutropenia and grade 1-2 anemia as positive predictors of OS. Multivariate analysis describes similar results (Table). Conclusions: Japanese series (Yohei Nose, et al; Katsuya Makihara, et al and T. Yoshino, et al) suggest a benefit in OS directly proportional to the degree of neutropenia found. In our study we obtain similar results, with better OS results for patients with grade 3-4 neutropenia. Therefore, we consider severe neutropenia as a possible predictor of the efficacy of TAS-102. Although our series is one of the largest published to date, we need more studies with a larger sample to obtain robust and enlightening results.[Table: see text]